Evidence
Alert

More precise classification of risk in prostate cancer reveals a huge variation in treatment

A new study found a wide variation in how men with prostate cancer are managed in different hospitals. Current NICE guidelines recommend that prostate cancers are broadly classified into those at low, intermediate or high risk of spreading. A more precise system for classifying risk revealed that hospitals may have different approaches for managing men with intermediate-risk cancer.

Men who have prostate cancer which is likely to grow quickly (high-risk) receive radiotherapy or surgery to control their disease. But these treatments can damage sexual function and/or continence. To avoid unnecessary treatment, men with a low risk of their cancer growing are usually offered regular monitoring with blood tests and examinations (active surveillance), rather than radiotherapy or surgery.

This study has implications for men with intermediate-risk cancer. It found that in some hospitals, almost all are offered radiotherapy or surgery. In other hospitals, they are much more likely to be monitored with active surveillance and spared the possible effects of treatment.

What’s the issue?

More than 48,500 men are diagnosed with prostate cancer each year in the UK. Doctors use a combination of blood tests, scans and laboratory results to judge how likely the cancer is to spread. This assessment of risk guides decisions about treatment.

Current NICE guidelines classify prostate cancers in three tiers: low, intermediate or high risk. These are broad tiers, and not all men in the intermediate group are at the same risk of their cancer spreading. Therefore, some can potentially avoid treatment.

The Cambridge Prognostic Group (CPG) classification splits both intermediate- and high-risk groups in two, giving five tiers in total. Intermediate-risk cancers are divided into tumours with favourable and unfavourable outlooks.

Previous research suggests that men with favourable intermediate-risk cancers do as well as men with low-risk cancers if managed with active surveillance. This study aimed to find out how men in these risk groups are currently being treated in hospitals around the country.

What’s new?

The study included 61,999 men diagnosed with prostate cancer in 129 English hospitals between 2014 and 2017. They split the men into five risk groups according to the CPG classification.

As expected, men in the low-risk group were least likely to have been treated with surgery or radiotherapy and most likely to have been on active surveillance. Men in the higher risk groups were most likely to have had surgery or radiotherapy. Variation between different hospitals’ approaches is not obvious in the broad intermediate category used by NICE. But when the researchers used the more detailed, five-tier CPG classification, they were able to consider those with favourable and unfavourable outlooks separately.

They found huge variations between hospitals in the treatments offered to men with intermediate-risk cancer. This was especially true for men with favourable intermediate-risk cancer. In some hospitals, less than a quarter of these men (23%) had surgery or radiotherapy. In others, almost all (97%) had surgery or radiotherapy. This suggests there is little agreement between hospitals in how these men should be managed.

Why is this important?

Use of the five-tier system revealed different approaches to treatment across the country. These differences may be particularly important for men with favourable intermediate-risk cancer. While some hospitals are using active surveillance for these men, in others almost all are receiving surgery or radiotherapy. This suggests that some of these men could have been managed with active surveillance and avoided the possible side effects of treatment.

What’s next?

NICE issued guidelines in 2019 which used the traditional three groupings of low-, intermediate- and high-risk prostate cancer. The guidelines do not divide intermediate-risk cancers into favourable and unfavourable groups. NICE recommends that men with intermediate-risk cancers should be offered surgery or radiotherapy.

Despite growing evidence in favour of active surveillance for favourable intermediate-risk prostate cancer, this approach is not recommended by NICE as initial treatment. But the guidelines state that it can be considered for men who choose not to have immediate radical treatment.

This work suggests that some men who received treatment for prostate cancer could have been managed with active surveillance.

You may be interested to read

The full paper: Parry MG, and others. Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation. BMC Medicine 2020;18:114

Zelic R, and others. Predicting Prostate Cancer Death with Different Pretreatment Risk Stratification Tools: A Head-to-head Comparison in a Nationwide Cohort Study. Eur Urol. 2020;77:180-188

Gnanapragasam VJ, and others. Improving clinical risk stratification at diagnosis in primary prostate cancer: a prognostic modelling study. PLoS Med. 2016;13: e1002063

Gnanapragasam VJ, and others. The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study. BMC Med. 2018;16:31.

The current National Institute for Health and Care Excellence (NICE) guidelines on management of prostate cancer: Prostate cancer: diagnosis and management NG131. May 2019

National Prostate Cancer Audit (NPCA) website, which summarises the reports of the NPCA and has useful information about prostate cancer treatment

Funding

The study was funded by an NIHR doctoral research fellowship.

Commentaries

Study author

The Cambridge Prognostic Group (CPG) five-tier classification system was derived from survival data from large scale studies (including over 80,000 men across 3 countries). Survival predictions from the CPG system have been shown to be much better than the current three-tiered system used in the UK or indeed other common classification systems used internationally.

Applying the CPG system in this work highlighted the large variation across the country in how men with intermediate-risk disease are managed. There are a number of men receiving treatment for their prostate cancer who could have been effectively managed with active surveillance. It will be important for guidelines in the future to make a distinction between favourable and unfavourable intermediate-risk prostate cancer and highlight how active surveillance can be used in this group.

Use of active surveillance should always be a joint decision between doctor and patient, taking into account individual circumstances, risks and preferences. I hope that this work can encourage clinicians to consider active surveillance more widely and, more importantly, to include patients within the decision-making process.

Matthew Parry, Urology Registrar and PhD researcher, London School of Hygiene and Tropical Medicine

Epidemiologist

This study is useful in giving more nuanced information about men at intermediate-risk prostate cancer. It showed that the current three levels of risk – low, intermediate and high – is crude. This study is a step towards distinguishing between favourable and unfavourable cancers of intermediate-risk and might encourage more detailed reporting and collection of national data.

The research was based on an extremely large dataset of 61,999 men but it was essentially a retrospective study looking back at national audit data to assess clinical decisions. What would help now would be to test the five-tier risk grouping in a real-world setting in which the risk grouping guides conservative or radical treatment choices. Ideally, the five-tier classifier would be tested against the current three-tier classifier in a randomised controlled trial. Metastases or deaths from prostate cancer would be the main outcome.

Richard Martin, Professor of Clinical Epidemiology, University of Bristol

Conflicts of Interest

None declared.